3-alkoxyphthalides



United SW35 gc 2,840,569 S-ALKOXYPHTHALIDES Donald 'DQWheeler and David C.Youug,lvfidland, Mich, assignors to The Dow Chemical Company, Midland, Mich., a-cor'poration of Delaware No Dl'awing. Application April 30, 1956 Serial No. 581,336

6Claims. (Cl. 260-3433) This invention is concerned with ph'thalides having the formula In this and succeeding formula'e, R represents a lower alkyl radical containing from 4 to .8 carbon atoms, in-

clusive, and X is -a member of the group consisting of chlorine and hydrogen. This invention also includes a method for preparing these compounds. The new compounds are colorless or amber liquids or low melting solids which are soluble in many common organic solvents such as benzene, toluene and acetone and are substantially insoluble in water. They are active as 'parasitic'ides and are adapted to be employed for the control "Of nematodes.

The new phthalide compounds may be obtained by I causing a phthalaldehydic acid having the formula to reactwith an alcohol having the formula, ROH, to=obtain the desired product and Water of reaction; The terms phthalaldehydic acid and El-hydroxyphthalide are employed interchangeably herein to refer to ta-compound having the structure Phthala'ld'ehydic acid is often represented in the literature as having the structure CHO COOH

ice

In the synthesis, good results are obtained when substantially 'equimolar proportions of the reactants are employed although "reasonable excesses of either reactant are operable. Phthalaldehydic acid, if used in large excess or under -conditions of high temperature, may form an anhydride by-product. The reaction takes place smoothly at temperatures of from 15 to 150 C. although a'rangeof from'90" to 120 C. is considered pref- ;erab1e fromthe standpoint of rate ofr'eaction and convenience 'of operation. Solvents such as benzene and toluene maybe employ'eizlfa's a reaction medium, if desired. The productobtained may be separated fromthe water of reaction by vapori'zationofth'elatter.

In a preferred method of carrying out the reaction, phthalaldehydic acid and an equirnolar proportion or an excess of the appropriate hydroxy compound are mixed and heated until the mixture begins to reflux and thereafter maintained at reflux temperature for from 0.5 to 7 hours. 'The mixture may then be heated at atmospheric pressure to distill unreacted alcohol. The reaction mixture is then poured into Water whereupon an insoluble oil precipitates. product and the latter washed with warm Water. The product, if a liquid, is dissolved in benzene and the-resulting solution distilled to remove any remaining water as a benzene-water azeo't'rope and residual solventLThe' remaining oily productmay be further purified, if desired, by fractional distillation under reduced pressure.-

In an alternative method, .phthalaldehydic acid and an equimolar proportion or an excess of the appropriatealcohol are mixed and heated from 120. to 150? C. for 1 to 3.h'ours. The pressure of the system is then reduced and the water of reaction removed by distillation. The crude product is obtained as a residue and, if desired, may be purified by distillation under reduced pressure.

The following examples illustrate the invention, but are ifnot to be'construetl 'asjlirniting. v

Example l.-3-sec0ndary but0xyphtlialide o-eecn...

milliliters (-3.0 moles) 'of secondary Ebutyl alcohol were mixed andheated .at the boiling temperature-under reflux for 7 hours, The mixture was. distilled to remove the unreacted secondary butyl :alcohol and the residue pouredinto water whereupon two layers formed. The water was decanted and the remaining oil dissolved in benzene.v The resultingbenzene solution was Washed with water, and the benzene recoverediby distilling under treduc'ed pressure to obtain*a 3-5econdarybutoxyphthalide OCH2 The wateris decanted from the oil or solid phthalaldehydic acid.

150 grams 1.0 mole)"ofphthalaldehydic acid and 300 milliliters (3.0 moles)fof isobutyl alcohol were mixed and heatedat reflux temperature for 7 hours. At the end ofthisperiod, the mixture was distilled to :remove the unreactcd isobutyl alcohol. .The remaining solution j was" cooled to about 80 C." and poured into] water whereupon two layersformed. The waterflwas decanted and the remainingoil repeatedly washed withlwater. The eombinedpwashings were extractedwith benzene. benzene extract and oil were combined and distilled under reduced 'pressure'to remove waterandbenzene.

The

The residue therefrom was fractionally distilledto obtain a T3-isobutoxyphthalide product boiling from 175 9 to 178 C. at 17 millimeters pressure and having a refractiveindex nbfiof 15109. The yield of the product was 156.5

grams or76perccnt of theoretical.

' em 3.- -3-no'rmal.-octyloxyphthalide "otonmcm t 150 (1.0 mole) 0: hthalaldehydieacidand 360 "milliliters (1.89 moles) of normal-oetyl alcohol were mixed and heated at reflux temperature for ,7 hours. The resulting crudeproduct was heated to remove water and unreacted octyl alcohol, and to' obtain a 3-normal-octyloxyphthalide product as an oily residue. The latter was purified ,by reduced pressure, distillation. The desired compound was a fraction boiling from 172 to 177 C. at 4 millimeters pressure and had a refractive index n Example 4 f I Insimilar'preparations, the-following derivatives were obtained from the reaction of aliphatic alcohols with Example 5 1 93 grams (0.5 mole) of x-chlorophthaldehydic acid (a phthalaldehydic acid containing achlorine atom in the aromatic ring) and 150'millilite'rs (0.95 mole) of octyl alcohol were mixed and heated to from 110 to 115 C. and under reflux for 7 hours; The mixture was then heated under reduced pressure to vaporize water and unreacted octyl alcohol and-to obtain as residue a 3-octyloxy-xchlorophthalide product. The latter W'as'fractionally distilled at reduced pressure to recover apurified product boiling from 187 to 207 C. at6 millimeters pressure.

of tertiary-butyl alcohol and V p In similar preparation, the following lower alkoxyphthalides are prepared.

3-normal-heptyloxyphthalide by the reaction of phthalaldehydic acid and normal-heptyl alcohol. 5 3-normal-pentyloxyphthalide by the reaction of phthalaldehydic acid and normal-pentyl alcohol.

3-tertiary-butoxy;x-chlorophthalide by the reaction of x-chlorophthalaldehydic acid and tertiary'butyl alcohol.

3-isobutoxy-x-chlorophthalide, by the reaction of xchlorophthalaldehydicacid and isobutyl alcohol. 7

3-normal-hexyloxy-x-chlorophthalide by the reaction of x-chlorophthalaldehydic acid and normal-hexyl alcohol.

The products of this invention are useful for the control of the larvae of rootknot nematodes. In a representative operation,-3-normal-octyloxyphthalide was dispersed in water to prepare a composition containing 10 parts of phthalide per million parts of dispersion. This composition gave good control of larvae of the -rootkn ot nematode (Meloidogyne species) contacted therewith.

The phthalaldehydic acid employed in this invention may be prepared by first photochlorinating o-xylene to obtain u,,u,e',u-pentachloro-ofxylene by passing chlorine gas into o-xylene while illuminating with sun lamps. The resulting chlorinated o-xylene is then heated with aqueous constant-boiling hydrochloric acid and ferric chloride solution, as more fully disclosed and claimed in a copending application of James D. Head and Owen D.

Ivins, Serial Number 279,682, filed March. 31, 1952, now

Patent No. 2,748,162. 1 a p a 30 The x-chlorophthalaldehydic-acid employed in this invention maybe prepared by first chlorinating o-xylene in the presence of ferric chloride in ,the temperature range of from 5' to C. to obtain a ring-chlorinated product, x-chloro-o-xylene. The ring chlorinated product is then photo-chlorinated to obtain a,a,oz,ot',ot'-XheXaChl0r0-O- xylene and the latter hydrolyzed in a manner similar to that described above for phthalaldehydic acid.

We claim: 0 1. The phthalide having the formula wherein R represents a lower alkyl radical containing from 4 to 8 carbon atoms, inclusive, and X is a member of the group consisting of chlorine and hydrogen. 2. 3 secondary-butoxyphthalide.

3. 3-isobutoxyphthalide.

4. 3-normal-butoxyphthalide. 5. 3-tertiary-butoxyphthalide.

6. 3-normal-octyloxyphthalide.

References Cited in the file of this patent Grove: Biochem. J., 54 pp., 664-673 (1953). so Racine: Annalen, vol. 239, page 83 (1887).

Auwers et al.: Berichte 52, pp. 587, 596 (1919). Kohlrausch et al.: Berichte 77, page 471 (1944). 

1. THE PHTHALIDE HAVING THE FORMULAA 